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First-Generation Anticonvulsants

Phenytoin (Dilantin®)—This is one of the more commonly used agents and often is considered the first-line drug to treat partial and generalized tonic-clonic (grand mal) seizures and status epilepticus.

Phenytoin is thought to work by suppressing electrical activity in brain nerve cells. It can be given orally or intravenously (IV), and a newer form of the drug, fosphenytoin (Cerebryx®), can be injected into muscle. The oral form has the benefit of once-a-day dosing.

Phenytoin drug levels need to be monitored with liver function testing and a complete blood count (CBC). The therapeutic concentration recommended is between 10–20mg/L. Phenytoin interacts with many other medications, and its level can fluctuate when other drugs are taken.

Side effects associated with its use include:

• Anemia
• Excessive hair growth (hirsuitism/hypertrichosis)
• Imbalance
• Lethargy
• Overgrowth of the gums (gingival hyperplasia)
• Peripheral weakness (neuropathy) with long-term use

Carbamazepine (Tegretol®/Carbatrol®)—This drug is commonly prescribed for the treatment of partial and generalized tonic-clonic (grand mal) seizures. The mechanism by which it works is not well understood. In oral form, it can be taken 2 to 3 times a day; a recent development of the drug in sustained-release form allows for twice-a-day dosing.

Carbamazepine levels must be monitored. The recommended therapeutic level is between 8–12mg/L. Liver function tests and CBC also must be checked routinely. Carbamazepine can affect the levels of a number of other drugs in the body, and its level can fluctuate when other agents are taken.

Side effects include drowsiness, imbalance, nausea, anemia, and low, white blood cell count (neutropenia).

Phenobarbital —This drug is used to treat both partial and generalized seizures. It also is used as part of the protocol after phenytoin use in status epilepticus as well as in neonatal epilepsy. It is available in oral and intravenous forms.

Levels need to be monitored. The recommended therapeutic level is 15–40mg/L. A complete blood analysis also should be routinely conducted. Phenobarbital can cause changes in the metabolism of other drugs through its actions on liver enzymes.

Possible side effects include drowsiness, cognitive impairment, and irritability.

Valproate (Depakote®)—This is prescribed for partial seizures, generalized tonic-clonic (grand mal) seizures, absence (petit mal) seizures, and myoclonic epilepsy. It also is approved to prevent migraine headaches. Its mechanism of action is thought to be related to the effect of a brain substance known as GABA (gamma-aminobutyric acid). It is available in oral form and must be taken 2 to 3 times per day for adequate dosing. An extended release form (Depakote® ER), which is taken once per day, is also available.

Drug levels must be monitored, as well as liver function and blood count. The drug's suggested therapeutic window is 50–100mg/L. Side effects include liver damage (hepatotoxicity), nausea, weight gain, hair loss (alopecia), and tremor.

Ethosuximide (Zarontin®)—This agent is used to treat absence (petit mal) seizures. It is thought to work by suppressing brain cell activity that is associated with lapses of consciousness. It is given orally and is available as a tablet or flavored syrup.

Ethosuximide levels need to be monitored to ensure that the therapeutic concentration of 40 to 100 mcg/mL is maintained. Complete blood count (CBC), urinalysis, and liver function tests also should be performed routinely to monitor for possible adverse effects.

Potential side effects produced by ethosuximide include the following:

• Gastrointestinal–nausea and vomiting, abdominal pain, cramps, diarrhea, weight loss
• Genitourinary–vaginal bleeding, blood in urine (microscopic hematuria)
• Hematological–bone marrow suppression
• Integumentary–excessive hair growth (hirsutism ), skin rash, systemic lupus erythematous (SLE)
• Neurological–headache, dizziness, sleep disturbances, aggression, incoordination, fatigue, inability to concentrate

Primidone (Mysoline®)—This drug is a barbiturate that contains phenobarbitol. It is used to control generalized tonic-clonic (grand mal) seizures and partial seizures and is used in adults and children over 8 years old.

The effective concentration of primidone in the body is 5-12 mcg/mL. This is achieved with 250 mg tablets taken 3 to 4 times daily. The dosage may be increased, but should not exceed 500 mg taken 4 times daily.

Potential side effects include:

• Blurred vision
• Fatigue
• Incoordination
• Nausea and vomiting
• Sexual impotence (erectile dysfunction)
• Vertigo
• Weight loss

Primidone is not known to interact with other drugs. It is present in breast milk and is associated with neonatal hemorrhage and coagulation defects similar to vitamin K deficiency. Patients hypersensitive to phenobarbital should not take primidone.

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